Chemical chaperone TUDCA rescues Insulin-mediated vascular relaxation via ER stress inhibition in diabetic rat model.

IF 1.9 4区医学 Q4 ENDOCRINOLOGY & METABOLISM

Endocrine Research Pub Date : 2026-08-01 Epub Date: 2026-04-16 DOI:10.1080/07435800.2026.2659582

Sagir Mustapha, Ahmad Khusairi Azemi, Aida Hanum Ghulam Rasool, Siti Safiah Mokhtar

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引用次数: 0

Abstract

Background: Tauroursodeoxycholic acid (TUDCA) has been shown to improve endothelial dysfunction in type 2 diabetes mellitus (T2DM). However, its role in attenuating endothelial insulin resistance in diabetes is not well understood.

Objectives: This study aimed to investigate TUDCA's potential therapeutic effect on endothelial insulin resistance and its underlying mechanisms.

Methods: Twenty-seven male Sprague Dawley rats were categorized into control (CON, n = 9), diabetes (DM, n = 9), and diabetes treated with TUDCA (DMT, n = 9). Diabetes was induced using a high-fat diet and low-dose streptozotocin. TUDCA (150 mg/kg) was administered to the DMT group during the last two weeks of a 15-week study. Aortic tissues were analyzed for insulin-mediated relaxation, endoplasmic reticulum (ER) stress markers [inositol-requiring kinase 1 (IRE-1), protein kinase-like ER kinase (PERK), and binding immunoglobulin protein (BIP)], end othelial function markers [endothelial nitric oxide synthase (eNOS), protein kinase B (Akt), and insulinreceptor substrate-1 (IRS-1)], oxidative stress [superoxide dismutase activity (SOD) and malondialdehyde level (MDA)] and inflammation [tumor necrosis factor-alpha (TNF-a)] markers.

Results: Insulin-mediated relaxation was impaired in diabetic rats (-56.7%) compared to controls (0%), accompanied by elevated ER stress markers and reduced eNOS, Akt, and IRS-1 expression. TUDCA treatment improved relaxation responses (-6.2%) significantly reduced ER stress markers and restored the expression of endothelial markers.

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化学伴侣TUDCA通过内质网应激抑制糖尿病大鼠模型恢复胰岛素介导的血管松弛。

背景：牛磺酸去氧胆酸（TUDCA）已被证明可改善2型糖尿病（T2DM）的内皮功能障碍。然而，其在减轻糖尿病内皮胰岛素抵抗中的作用尚不清楚。目的：本研究旨在探讨TUDCA对内皮胰岛素抵抗的潜在治疗作用及其机制。方法：27只雄性Sprague Dawley大鼠分为对照组（CON, n = 9）、糖尿病组（DM, n = 9）和糖尿病组（DMT, n = 9）。采用高脂肪饮食和低剂量链脲佐菌素诱导糖尿病。在为期15周的研究的最后两周，DMT组给予TUDCA （150 mg/kg）。分析主动脉组织中胰岛素介导的松弛、内质网（ER）应激标记物[肌醇需要激酶1 （ir -1）、蛋白激酶样ER激酶（PERK）和结合免疫球蛋白蛋白（BIP）]、终皮功能标记物[内皮型一氧化氮合酶（eNOS）、蛋白激酶B （Akt）和胰岛素受体底物-1 (IRS-1)]。氧化应激[超氧化物歧化酶活性（SOD）和丙二醛水平（MDA）]和炎症[肿瘤坏死因子- α (TNF-a)]标志物。结果：与对照组（0%）相比，糖尿病大鼠胰岛素介导的松弛功能受损（-56.7%），并伴有内质网应激标志物升高，eNOS、Akt和IRS-1表达降低。TUDCA治疗改善松弛反应（-6.2%），显著降低内质网应激标志物，恢复内皮标志物的表达。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine Research 医学-内分泌学与代谢

CiteScore

4.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： This journal publishes original articles relating to endocrinology in the broadest context. Subjects of interest include: receptors and mechanism of action of hormones, methodological advances in the detection and measurement of hormones; structure and chemical properties of hormones. Invitations to submit Brief Reviews are issued to specific authors by the Editors.